Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib

The combination of osimertinib with savolitinib in this study (the SAVANNAH study) will explore if the combination will overcome MET-amplification as a mechanism of resistance. The SAVANNAH study will investigate the efficacy of osimertinib in combination with savolitinib in participants with EGFRm+ and MET-amplified/overexpressed, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib. Eligible participants will be those with histologically or cytologically confirmed diagnosis of EGFRm+, MET amplified/overexpressed (≥10 MET gene copies by fluorescence in situ hybridisation \[FISH10+\] and/or ≥90% of tumour cells staining at 3+ intensity by immunohistochemistry \[IHC90+\]) NSCLC that is locally advanced or metastatic and is not amenable to further surgery or radiotherapy with curative intent. The disease must have progressed following treatment with first line osimertinib. Participants must have confirmation of MET-amplified/overexpressed tumour by central fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) testing (requirements summarised in the main body of the protocol and fully explained in the Central Laboratory Manual). Participants must not have received prior or current treatment with savolitinib or another MET inhibitor. All participants confirmed as eligible will begin treatment on Day 1 with osimertinib + savolitinib combination therapy or placebo to osimertinib + savolitinib. Treatment will continue in 28 day cycles until either objective disease progression by investigator per RECIST 1.1 is assessed, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.